Method of measuring and analyzing ocular response in a subject using stable pupillary parameters with video oculography system

ABSTRACT

A method of measuring and analyzing an ocular response in a subject comprising the steps of: Providing a video oculography based system for the subject with the system configured to collect eye images in excess of 60 hz and configured to resolve eye movements smaller than at least 3 degrees of motion; Collecting eye data with the video oculography based system wherein at least one stimulus is presented to only one eye of the subject and configured to yield a pupil eye response from at least one eye of the subject; Calculating pupilometry measurements from the eye data, wherein the pupil measurements are calculated independently for the subject&#39;s left and right eyes for each stimulus presented to the subject, and wherein comparative left and right pupilometry measurements from the eye data are calculated; analyzing a subject&#39;s ocular response based upon at least one of the calculated pupilometry measurements.

RELATED APPLICATIONS

The present application is a divisional of U.S. application Ser. No.14/216,480, filed Mar. 17, 2014, entitled “Method of Measuring andAnalyzing Ocular Response in a Subject Using Stable Pupillary Parameterswith Video Oculography System” which published Oct. 23, 2014 as U.S.Patent Publication number 2014/0313488, and issued as U.S. Pat. No.9,198,571 on Dec. 1, 2015 and this publication and patent isincorporated herein by reference.

U.S. application Ser. No. 14/216,480 claims the benefit of U.S.provisional application Ser. No. 61/799,959 entitled “Method andApparatus for Objective Ophthalmic Eye Testing in Video-OculographyApplications” filed Mar. 15, 2013.

U.S. application Ser. No. 14/216,480 claims the benefit of U.S.provisional application Ser. No. 61/918,243 entitled “High Speed VOGSynchronization For Head Mounted VOG System With Onboard Display AndCompact Integrated Optics And Hot Mirror Unit” filed Dec. 19, 2013.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to testing procedures in ophthalmic eyetesting with eye trackers, such as in video-oculography systems, andmore specifically to pupil testing procedures.

2. Background Information

A standard ophthalmic exam is a series of tests done to check asubject's vision and the health of the subject's eyes. Included in thistesting are standard tests used to check visual acuity, pupil function,eye movement and peripheral vision. The basic format or operation ofthese tests are well known to the practitioners the field, some general(overlapping) categories used in the field to broadly describe suchtesting includes eye movement tests, visual acuity tests, Pupillometrytests, nystagmus tests, smooth pursuit tests, saccades tests,optokinetic tests, peripheral vision testing, subjective visualhorizontal and subjective visual vertical tests.

Visual acuity tests may be performed in many different ways. It is aquick way to detect vision problems and is frequently used in schools orfor other mass screening, e.g. military recruits. Driver license bureausoften use a small device that can test the eyes both together andindividually.

Pupillometry tests represent conventional examination of pupillaryfunction includes inspecting the pupils for equal size (1 mm or less ofdifference may be normal), regular shape, reactivity to light, anddirect and consensual accommodation. A swinging flashlight test is oneknown pupillometry test which may also be desirable if neurologic damageis suspected. In a normal reaction to the swinging-flashlight test, bothpupils constrict when one is exposed to light. As the light is beingmoved from one eye to another, both eyes begin to dilate, but constrictagain when light has reached the other eye.

Eye movement testing can also be called extra-ocular muscle functiontesting is an examination of the function of the eye muscles. Thesetests observe the movement of the eyes in six specific directions.

Peripheral vision testing is also called visual field testing. It hasbeen suggested that evaluation of the visual fields should never beomitted from the basic eye examination. Testing the visual fieldsconsists of confrontation field testing in which each eye is testedseparately to assess the extent of the peripheral field.

In many of the above testing, namely check visual acuity, pupilfunction, eye movement and peripheral vision, testing apparatus havebeen developed to automatically supply the appropriate visual stimulusto the subject to conduct the test. Further, these devices can be foundin desk mounted arrangements which accommodate the subjects head, wallor desk mounted units (e.g. monitors) that provide that the subject is afixed distance away typically in a chair, chair mounted projection typeunits mounted on the subjects chair that project onto the wall, and evenhead mounted units attached to the subject.

Within the meaning of this application any ophthalmic eye testing devicethat supplies a predetermined visual stimulus to the subject in apredetermined location (which may move) is an automated ophthalmic eyetesting device. One such automated ophthalmic eye testing device is thelaser based PURSUIT TRACKER® system of visual stimulus generatoravailable from the applicant, Neuro-Kinetics, Inc. This type of device,and some of the testing that can be performed with such devices, isdescribed in U.S. Pat. Nos. 7,651,224 and 8,333,472 which areincorporated herein by reference. Additionally the ophthalmic eyetesting device may be incorporated with an eye tracker such as describedin U.S. Pat. No. 8,585,609 which is incorporated herein by reference.

Eye trackers measure eye movement, i.e. rotations of the eye, in one ofseveral ways, but principally they fall into three categories:

One category of eye tracker uses an attachment to the eye, such as aspecial contact lens with an embedded mirror or magnetic field sensor,and the movement of the attachment is measured with the assumption thatit does not slip significantly as the eye rotates. Measurements withtight fitting contact lenses have provided extremely sensitiverecordings of eye movement, and magnetic search coils are the method ofchoice for researchers studying the dynamics and underlying physiologyof eye movement.

A second category of eye tracker uses electric potentials measured withelectrodes placed around the eyes. The eyes are the origin of a steadyelectric potential field, which can also be detected in total darknessand if the eyes are closed. It can be modeled to be generated by adipole with its positive pole at the cornea and its negative pole at theretina. The electric signal that can be derived using two pairs ofcontact electrodes placed on the skin around one eye is calledElectro-oculogram (EOG). If the eyes move from the center positiontowards the periphery, the retina approaches one electrode while thecornea approaches the opposing one. This change in the orientation ofthe dipole and consequently the electric potential field results in achange in the measured EOG signal. Inversely, by analyzing these changesin eye movement can be tracked. Due to what is known as thediscretization given by the common electrode setup two separate movementcomponents—a horizontal and a vertical—can be identified. The potentialdifference is not constant and its variations make it challenging to useEOG for measuring slow eye movement and detecting gaze direction. EOGis, however, a very robust technique for measuring saccadic eye movementassociated with gaze shifts and detecting blinks. It is a verylight-weight approach that, in contrast to current video-based eyetrackers, only requires very low computational power, works underdifferent lighting conditions and can be implemented as an embedded,self-contained wearable system. It is thus the method of choice formeasuring eye movement in mobile daily-life situations and REM (RapidEye Movement) phases during sleep.

The third broad category of eye tracker, which is the category relevantto the present invention, uses some non-contact, optical method formeasuring eye motion. Generally these are video based eye trackers.Light, typically infrared, is reflected from the eye and sensed by avideo camera or some other specially designed optical sensor. Theinformation is then analyzed to extract eye rotation from changes inreflections. One class of video based eye trackers typically uses thecorneal reflection (the first Purkinje image) and the center of thepupil as features to track over time. A more sensitive type of eyetracker, the dual-Purkinje eye tracker, uses reflections from the frontof the cornea (first Purkinje image) and the back of the lens (fourthPurkinje image) as features to track. A still more sensitive method oftracking in this class is to image features from inside the eye, such asthe retinal blood vessels, and follow these features as the eye rotates.Other video systems digitize the eye and locate the pupil in the imageand utilize object recognition analysis or processing to locate andtrack the pupil in the digitized image. Optical methods, particularlythose based on video recording, are widely used for gaze tracking andare favored for being non-invasive and inexpensive.

With this general background, the problems addressed by the presentclaimed invention can be described. Conventional pupilometry fails toprovide sufficient or the most relevant pupil related data. Conventionalpupilometry measurements in the art include generally the amplitude ofthe change to pupil size (diameter), i.e. what is the size of the pupilafter stimulation or after the stimulation is removed, or even morebasically some systems only identify whether such a change is occurringat all. Further some pupilometers identify the latency of the response.There is a need in the art, especially in automated testing systems, formethod of measuring and analyzing an ocular response in a subjectproviding more stable pupilometry parameters and more meaningfulpupilometry parameters.

SUMMARY OF THE INVENTION

One aspect of the present invention provides a method of measuring andanalyzing an ocular response in a subject comprising the steps of: A)Providing a video oculography based system for the subject with thevideo oculography system configured to collect eye images of the subjectin excess of 60 hz and configured to resolve eye movements smaller thanat least 3 degrees of motion; B) Collecting eye data with the videooculography based system wherein at least one stimulus is presented tothe subject and configured to yield a pupil eye response from at leastone eye of the subject; C) Calculating pupilometry measurements from theeye data including at least one of: i) average pupil constrictionvelocity for subject's eyes, wherein the average pupil constrictionvelocity for subject's eyes is the average of the subject's eyes totalamplitude of pupil constriction following a stimulus display divided bythe length of time the associated pupil is undergoing constrictionfollowing the stimulus display; ii) average pupil dilation velocity forsubject's eyes, wherein the average pupil dilation velocity forsubject's eyes is the average of the subject's eyes total amplitude ofpupil dilation following a stimulus display divided by the length oftime the associated pupil is undergoing dilation following thetermination of a stimulus display; iii) maximum pupil constrictionvelocity for subject's eyes, wherein the maximum pupil constrictionvelocity for subject's eyes is the maximum calculated pupil constrictionvelocity of the subject's eyes following a stimulus display; iv) maximumpupil dilation velocity for subject's eyes, wherein the maximum pupildilation velocity for subject's eyes is the maximum calculated pupildilation velocity of the subject's eyes following the termination of astimulus display; v) pupil constriction acceleration for subject's eyes,wherein the pupil constriction acceleration for subject's eyes is therate of change of the calculated pupil constriction velocities followingthe stimulus display; vi) pupil dilation acceleration for subject'seyes, wherein the pupil dilation acceleration for subject's eyes is therate of change of the calculated pupil dilation velocities following thetermination of a stimulus display; vii) at least one pupil saturationparameter, wherein each pupil saturation parameter for subject's eyes isa physiologic measurement associated with pupil dilation velocity whenthe eye is subjected to a stimulus of a given illumination; and D)analyzing a subject's ocular response based upon at least one of thecalculated pupilometry measurements of step C.

Another aspect of the present invention provides a method of measuringand analyzing an ocular response in a subject comprising the steps of:A) Providing a video oculography based system for the subject with thevideo oculography system configured to collect eye images of the patientin excess of 60 hz and configured to resolve eye movements smaller thanat least 3 degrees of motion; B) Collecting eye data with the videooculography based system wherein at least one stimulus is presented toonly one eye of the subject and configured to yield a pupil eye responsefrom at least one eye of the subject; C) Calculating pupilometrymeasurements from the eye data, wherein the pupil measurements arecalculated independently for the subject's left and right eyes for eachstimulus presented to the subject, and wherein comparative left andright pupilometry measurements from the eye data are calculated; and D)analyzing a subject's ocular response based upon at least one of thecalculated pupilometry measurements of step C.

Another aspect of the present invention provides a method of measuringand analyzing an ocular response in a subject comprising the steps of:A) Providing a video oculography based system for the subject with thevideo oculography system configured to collect eye images of the patientin excess of 60 hz and configured to resolve eye movements smaller thanat least 3 degrees of motion; B) Collecting eye data with the videooculography based system wherein at least one stimulus is presented tothe subject and configured to yield a pupil eye response from at leastone eye of the subject; C) Calculating pupilometry constrictionmeasurements from the eye data including at least one of: i) averagepupil constriction velocity for subject's eyes, wherein the averagepupil constriction velocity for subject's eyes is the average of thesubject's eyes total amplitude of pupil constriction following astimulus display divided by the length of time the associated pupil isundergoing constriction following the stimulus display; ii) maximumpupil constriction velocity for subject's eyes, wherein the maximumpupil constriction velocity for subject's eyes is the maximum calculatedpupil constriction velocity of the subject's eyes following a stimulusdisplay; iii) pupil constriction acceleration for subject's eyes,wherein the pupil constriction acceleration for subject's eyes is therate of change of the calculated pupil constriction velocities followingthe stimulus display; and iv) at least one pupil saturation parameter,wherein each pupil saturation parameter for subject's eyes is aphysiologic measurement associated with pupil dilation velocity when theeye is subjected to a stimulus of a given illumination; D) Calculatingpupilometry dilation measurements from the eye data including at leastone of: i) average pupil dilation velocity for subject's eyes, whereinthe average pupil dilation velocity for subject's eyes is the average ofthe subject's eyes total amplitude of pupil dilation following astimulus display divided by the length of time the associated pupil isundergoing dilation following the termination of a stimulus display; ii)pupil dilation acceleration for subject's eyes, wherein the pupildilation acceleration for subject's eyes is the rate of change of thecalculated pupil dilation velocities following the termination of astimulus display; and iii) maximum pupil dilation velocity for subject'seyes, wherein the maximum pupil dilation velocity for subject's eyes isthe maximum calculated pupil dilation velocity of the subject's eyesfollowing the termination of a stimulus display; and E) analyzing asubject's ocular response based upon at least one of the calculatedpupilometry constriction measurements of step C and one of thecalculated pupilometry dilation measurements of step D.

These and other advantages of the present invention will be described inconnection with the preferred embodiments that are disclosed inconnection with attached figures wherein like reference numeralsrepresent like elements throughout.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a schematic view of a subject wearing a head mounted videooculography system (VOG) system in accordance with one aspect of thepresent invention;

FIG. 2 is a schematic view of a head mounted open goggle based videooculography system (VOG) system in accordance with one aspect of thepresent invention;

FIG. 3 is a schematic view of a head mounted closed goggle based videooculography system (VOG) system with integral stimulus screen inaccordance with one aspect of the present invention;

FIGS. 4A and B are schematic views of a head mounted closed goggle basedvideo oculography system (VOG) system with integral stimulus screen inaccordance with one aspect of the present invention;

FIG. 5 schematically illustrates a visual fixation target for eyeevaluation applications requiring subject compliance with eye fixationto the visual fixation target and schematically illustrates validationthresholds and sample subject's calculated gaze positions;

FIGS. 6 and 7 are eye position graphs illustrating pupilometryparameters obtained for measuring and analyzing ocular response with thesystem according to one embodiment of the present invention;

FIG. 8 is an eye saturation graph illustrating pupilometry parametersassociated with pupil dilation velocities and stimulation illuminationwhich are obtained for measuring and analyzing ocular response with thesystem according to one embodiment of the present invention;

FIG. 9A-C schematically illustrate system synchronization configurationsfor use with the system according to one embodiment of the presentinvention;

FIGS. 10A-B schematically illustrates a video synchronization signal foruse with the system according to one embodiment of the presentinvention;

FIG. 11 illustrates an input device in the form of a rotary chair forperforming a saccade reaction time testing protocol according to oneembodiment of the present invention;

FIGS. 12A-F illustrate display results and control parameters associatedwith the saccade reaction time testing protocol according to oneembodiment of the present invention;

FIGS. 13A-B illustrate display results and control parameters associatedwith an objective anti-saccade test response testing protocol accordingto one embodiment of the present invention;

FIGS. 14A-D illustrate display results and control parameters associatedwith Predictive saccade response testing protocol according to oneembodiment of the present invention;

FIG. 15 illustrates display results and control parameters associatedwith a normal and abnormal response in a percent of saccade function ofa smooth pursuit testing protocol which may be utilized as an indicatorfor mTBI according to one embodiment of the present invention; and

FIGS. 16A-D illustrate display results and control parameters associatedwith video oculographic quantification of the fast phase optokineticstimulated nystagmus testing protocol according to one embodiment of thepresent invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The most widely used current eye tracker designs are video-based eyetrackers. Video-based eye trackers within the meaning of thisapplication are those systems obtaining visual images of the eyes. Someof these eye trackers have a convergence or gaze tracking function tocalculate where the subject is looking. This calculated gaze may, forexample, may be used as an input or control mechanism for other actions(e.g., such as proposed in certain heads up display (HUD) controlsystems. The record of the eye tracking has also been used to evaluateadvertizing materials and the like. More relevant to the presentinvention, the record of the eye tracking has also been analyzed for eyeevaluation purposes, which is generally the subject of the presentinvention. Video-based eye trackers are also known as Video-OculoGraphy(VOG) systems where the data obtained is used to analyze the subject'seyes and other physical attributes, as eye data has proven to bereliable biomarkers for various neurological conditions in addition toeye disorders (such as optical deficiencies in general, Oculomotor nervepalsy, Homer's syndrome, Blepharospasm, Ischemic optic neuropathy, andGlaucoma) including, but not limited to, mTBI, diabetes (diabeticretinopathy), Alzheimer's disease, Multiple Scoliosis (MS), andParkinson syndrome. FIG. 1 is representative of a subject 5 wearing aVOG system 10 while seated in chair 8 VOG systems are now a widely usedand accepted method to track and analyze eye movements, particularly forbalance and neuro-otologic testing.

For example, the Applicant, Neuro Kinetics, Inc. (NKI) has producedvideo-oculography systems that deliver accurate, affordable,4-dimensional eye measurement and analysis such as system 10 shown inFIG. 1. With Neuro Kinetics' I-PORTAL® brand VOG system 10 a wider rangeof clinicians and researchers have the opportunity to improve diagnosesand increase understanding of both the vestibular and neuro-ocular-motorsystems. These types of VOG systems 10 allow the world's leading VOGresearchers to view and evaluate real-time analysis of eye movement. Thepresent application is intended to give such researchers additionalobjective tools for carrying their work forward.

In general in such systems 10, a camera focuses on one or both eyes andrecords their movement as the viewer looks at some kind of stimulus.Most modem video based eye trackers use contrast to locate the center ofthe pupil and use infrared and near-infrared non-collimated light tocreate a corneal reflection (CR). The vector between these two featurescan be used to compute gaze intersection with a surface after a simplecalibration for an individual subject 5.

Two general types of eye tracking techniques are used in known eyetrackers: Bright Pupil and Dark Pupil. Their difference is based on thelocation of the illumination source with respect to the optics. If theillumination is coaxial with the optical path, then the eye acts as aretro-reflector as the light reflects off the retina creating a brightpupil effect similar to red eye. If the illumination source is offsetfrom the optical path, then the pupil appears dark because theretro-reflection from the retina is directed away from the camera.Bright Pupil tracking creates greater iris/pupil contrast allowing formore robust eye tracking with all iris pigmentation and greatly reducesinterference caused by eyelashes and other obscuring features. It alsoallows for tracking in lighting conditions ranging from total darknessto very bright. But bright pupil techniques are not effective fortracking outdoors as extraneous IR sources interfere with monitoring.

Video based eye tracker set ups vary greatly; some are head-mounted suchas the system 10, some require the head to be stable (for example, witha chin rest), and some function remotely and automatically track thehead during motion. Most use a sampling rate of at least 30 Hz, althoughthis minimizes the types of data that can be obtained as such a samplingrate is too slow for reasonably obtaining higher level eye movementparameters such as corrective saccades, micro-saccades (also calledmicro-tremors), and some pupillary responses. Thus 50/60 Hz is mostcommon, today while some video-based eye trackers run at 240 Hz, 350 Hz,500 Hz or even 1000/1250 Hz, which is needed in order to capture thedetail of the very rapid eye movement during eye evaluations, or duringstudies of neurology.

Eye movement itself is typically divided into fixations and saccades,when the eye gaze pauses in a certain position, and when it moves toanother position, respectively. The resulting series of fixations andsaccades is often called a scanpath. The central one or two degrees ofthe visual angle (the fovea) provide the bulk of visual information; theinput from larger eccentricities (the periphery) is less informative.Hence, the locations of fixations along a scanpath show what informationloci on the stimulus were processed during an eye tracking session. Onaverage, fixations last for around 200 ms during the reading oflinguistic text, and 350 ms during the viewing of a scene. Preparing asaccade towards a new goal takes around 200 ms.

Scanpaths are useful for analyzing cognitive intent, interest, andsalience. Other biological factors (some as simple as gender) may affectthe scanpath as well. Eye tracking in HCI typically investigates thescanpath for usability purposes, or as a method of input ingaze-contingent displays, also known as gaze-based interfaces.

VOG systems, such as system 10 shown in FIG. 1, often measure therotation of the eye with respect to the measuring system. If themeasuring system is a head mounted VOG system, such as system 10, theneye-in-head angles are measured. If the measuring eye tracking system istable mounted, as with scleral search coils or table mounted camera(“remote”) systems, then gaze angles are measured.

In many applications, the head position is fixed using a bite bar, aforehead support or something similar, so that eye position and gaze arethe same. In other cases, the head is free to move, and head movement ismeasured with systems such as magnetic or video based head trackers.

For head-mounted trackers, such as system 10, head position anddirection are added to eye-in-head direction to determine gazedirection. For table-mounted systems, such as search coils, headdirection is subtracted from gaze direction to determine eye-in-headposition.

Within the meaning of this application tracking the subjects gaze with avideo based eye tracker means the system is tracking where the subject'seyes are directed, typically relative to a fixation target or fixationstimulus.

A great deal of research has gone into studies of the mechanisms anddynamics of eye rotation, but the goal of eye tracking is most often toestimate gaze direction. Users may be interested in what features of animage draw the eye, for example, as advertisers have long used videobased eye trackers in connection with evaluation of specificadvertisements. It is important to realize that the typical eye trackerdoes not provide absolute gaze direction, but rather can only measurechanges in gaze direction. In order to know precisely what a subject islooking at, some calibration procedure is required in which the subjectlooks at a point or series of points, while the eye tracker records thevalue that corresponds to each gaze position. (Even those techniquesthat track features of the retina cannot provide exact gaze directionbecause there is no specific anatomical feature that marks the exactpoint where the visual axis meets the retina, if indeed there is such asingle, stable point.) An accurate and reliable calibration is essentialfor obtaining valid and repeatable eye movement data, and this can be asignificant challenge for non-verbal subjects or those who have unstablegaze.

Each method of eye tracking has advantages and disadvantages, and thechoice of an eye tracking system depends on considerations of cost andapplication. There is a trade-off between cost and sensitivity, with themost sensitive systems costing many tens of thousands of dollars andrequiring considerable expertise to operate properly. Advances incomputer and video technology have led to the development of relativelylow cost systems that are useful for many applications and fairly easyto use. Interpretation of the results still requires some level ofexpertise, however, because a misaligned or poorly calibrated system canproduce wildly erroneous data.

One difficulty in evaluating an eye tracking system is that the eye isnever still, and it can be difficult to distinguish the tiny, but rapidand somewhat chaotic movement associated with fixation from noisesources in the eye tracking mechanism itself. One useful evaluationtechnique is to record from the two eyes simultaneously and compare thevertical rotation records. The two eyes of a normal subject are verytightly coordinated and vertical gaze directions typically agree towithin +/−2 minutes of arc (RMS of vertical position difference) duringsteady fixation. Thus properly functioning and sensitive eye trackingsystem will show this level of agreement between the two eyes, and anydifferences much larger than this can usually be attributed tomeasurement error.

OBJECTIVE OPHTHALMIC EYE TESTING IN VIDEO-OCULOGRAPHY APPLICATIONS

As noted above, the present invention also relates to Video-oculographysystems 10, also called VOG systems 10. Video-oculographic recording ofeye movement has been shown to be a highly effective non-invasivetechnology for evaluating and analyzing eye movement. See the Richard E.Gans article in the May 2001, volume 54, pages 40-42 of The HearingJournal, which provide great insight to the beginning of practicalgoggle based VOG systems in 2001. Abnormalities of eye movement providevaluable information about the location of the dysfunction or diseaseprocess. Many abnormalities are specific to certain pathophysiology orpharmacologic influences. The advantage of recording/evaluating eyemovements versus other axial or limb musculature is that they are easierto interpret. Eye movement is limited to movement in three planes:horizontal, vertical, and rotational. Pupillary reactions (constrictionand dilation parameters) represent another category of parameters thatmay be desired to be tracked for certain applications.

VOG SYSTEM 10 OVERVIEW

Current VOG systems 10 that accurately track eye movement for diagnosticpurposes can be represented by those described in U.S. Pat. Nos.7,448,751, 7,520,614, 7,665,845, 7,731,360, 7,753,523, and 7,866,818 andU.S. Patent Application Publications 2005-0099601, 2007-0177103,2007-0132841, 2008-0049186, and 2008-0049187 which are incorporatedherein by reference. A further example of a current state of the art VOGsystem include the 2013 I-Portal® brand VOG systems from Neuro-Kinetics,Inc, which is a fully digital VOG system that delivers accurate 4D eyetracking. The lightweight goggle system is offered in standard 60 Hz and120 Hz goggle sets, both occluded and free field of view, althoughhigher speeds of 200 Hz, 250 Hz, 340 Hz and 500 Hz and even higher aremade available for particular applications. The speed of the system isdetermined by the cameras utilized and the higher speeds will generallyincrease the associated cost of the system 10.

The system 10 may be an open goggle VOG system such as schematicallyshown in FIG. 2 in which a pair of digital cameras 12 (for example,internal point firefly MV digital cameras, or XIMEA xiQ USB 25 HzDigital Cameras, etc) are mounted in goggle frame. The eyes of thesubject 5 are illuminated with infrared diodes 14 and the cameras 12obtain images of the illuminated eyes via hot mirrors 16 (such as fromEdmund Optics) directed. The system 10 includes onboard controls 14 forcontrolling the cameras 12 and illumination sources 14 and other itemssuch as a calibration laser or onboard stimulus. The system 10 furtherincludes head position sensor 18 (from CH robotics) which can supplyadditional physiologic position data in use. The sensor 18 is preferablya six degree of freedom sensor. The open design of system 10 of FIG. 2allows the subject to view targets and stimulus generated on otherequipment, such as a display screen or through use of a targetgenerating system such as the PURSUIT TRACKER® system of the applicant.

The system 10 may be a goggle based head mounted VOG system with onboarddisplay 22 such as schematically shown in FIG. 3. In FIG. 3 the VOGsystem includes an onboard display 22 that can be considered the same asa display in a cell phone of tablet computer. In this system 10 thedisplay 22 is used to display the fixation targets and stimulus to thesubject 5. The eyes 7 of the subject 5 have a view of the display 22 viahot minors 16 and optic 24.

Virtual reality technology will allow the display 22 to present targetsand stimulus and even whole environments to the subject 5 such that theyappear at any desired distance. For example, an eye chart displayed onthe display 22 can be generated to appear at a distance of 20 feet(standard ophthalmic eye testing distance for such test). The operationof the display 22 is known to those in the virtual reality applications.Much of the development in such technology has been driven by the gamingworld, such as Oculus VR, Inc. who is dedicated to the development ofimmersive “virtual reality technology that's wearable and affordable.”In most testing protocols the virtual reality simulations are quiterudimentary by the gamer standards as the stimulus is often a single dotor simple letter or symbol. However virtual reality currently availableallows the goggles of the system 10 of FIGS. 3 and 4A-B to immerse thesubject 5 into any desired scenario such that the testing protocols forthe system 10 of FIGS. 3 and 4A-B are not limited.

FIGS. 4A and B are schematic views of a head mounted closed goggle basedvideo oculography system 10 with integral stimulus screen 22 inaccordance with another aspect of the present invention. The system 10of FIGS. 4A and B uses a compact integrated optics 24 and hot mirrorunit 16 with top mounted cameras 12. The system 10 of FIGS. 4 A and Buses a single-screen 22 design shown in the FIGS. 4A and B that providesa head mounted goggle based VOG system 10 with onboard display 22 andcompact integrated optics 24 and hot minor unit 16. One key aspect ofthe design of system 10 of FIGS. 4A and B is using a first “camera”optic or lens 24 in front of the angled hot minor 12 and a separatedisplay optic or lens 24 behind the angled hot minor 12 that isassociated solely with the display 12. The display optics that transmitsthe image of display 22 to the subject's eye 7 is technically thecombination of the camera optic 24 and the display optics 24. Theseparate front and rear optics 24 as shown allows the system 10 toaccommodate the necessary camera field for cameras 12 and the displayfield for display 22 without undue distortion while remaining a compactsystem as shown. The compact system allows for simple gross adjustmentof the optic position relative to the user via a rack and pinionadjustment or similar adjustment.

OBJECTIVE OPHTHALMIC EYE TESTING IN APPLICATIONS REQUIRING SUBJECTCOMPLIANCE WITH EYE FIXATION

One aspect of the present invention provides a method for validatingtesting procedure in objective ophthalmic eye testing for eye evaluationapplications requiring subject compliance with eye fixation to a visualtarget 32 represented in FIG. 5. A representative test is peripheralvision testing in which the subject 5 is instructed to maintain gaze onthe visual target 32 and the subject 5 is then displayed visual indiciain his peripheral vision, which presumes the subject 5 is maintain gazeupon the fixation target 32 throughout the testing.

The predetermined visual fixation target 32 is supplied to the subject 5in a predetermined location with an automated ophthalmic eye testingdevice. The validation or compliance monitoring of the present inventionis utilized in testing procedure of the eye evaluation application whichrequires the subject 5 to fixate upon the visual fixation target 5, suchas peripheral vision testing. The display of the visual fixation target32 and the peripheral stimulus may be on display 22 in the closed gogglesystem 10 of FIGS. 4A and B. Alternatively in the open system 10 of FIG.3 the visual fixation target 32 may be generated by a separate displaysuch as a laptop computer display screen (directly or projected onto asurface in front of the subject 5), or formed by image generating systemsuch as the PURSUIT TRACKER® brand laser generating tool.

The system and associated method of the present invention includestracking the subject's gaze during at least the supplying of thepredetermined visual fixation target 32 to the subject 5 throughout thetesting procedure of the eye evaluation application with a video basedeye tracking system 10. Select gaze points 36 of the subject 5 are shownrelative to the fixation target 32 for illustration. The gaze points 36will not be randomly distributed but will generally form a scanpath asknown in the art and the three points 36 shown represent distinct points36 at spaced times along a scanpath for illustrative purposes.Additionally the present invention can compare each calculated gazepoint 36 with the associated threshold 34 within the period of time thesystem 10 is obtaining each relative data point, or alternatively acollection of gaze points 36 within a segment of time associated witheach relative data point maybe combined to form a single gaze point 36for that segment. The combining of gaze points 36 within a segment oftime could be by averaging all the gaze points 36 within a segment, or aweighted average, or by taking the maximum variation from the target 52as the gaze point 36 for that segment.

The system and associated method of the present invention includesvalidating the testing procedure by at least one of i) indicating to theclinician when the subject's gaze location 36 differs from thepredetermined visual fixation target 32 by an amount greater than apredetermined threshold amount 34, and ii) having the automatedophthalmic eye testing device repeat at least portions of the testingprocedures when the subject's gaze location 36 differs from thepredetermined visual fixation target 32 by an amount greater than apredetermined threshold amount 34. The system may do both the indicationto the clinician and the automatic rerunning of data.

The real time display to the clinician of the results and the record ofthe session will include a visual indication that selected data sets arenot validated due to failure of the subject's gaze 36 being within thedesired threshold. Many visual indicating methods may be implemented,such as toggling between informative text associated with the data, forexample VALID and INVALID, COMPLIANT and NONCOMPLIANT, nothing andFIXATION LOST and/or listing the associated difference between the gazepoint 36 and the fixation target 34. Color coding may be added whereinred is used to visually identify non-compliance data and greenillustrate validated data sets. Different indicators may be used ondifferent displayed elements, for example a red border surrounding therecorded image of the subjects eye may be used on that screen with textin the boarder, and in graphical representation of data, non-validateddata sets may simply be omitted from the graph or highlighted in red orotherwise identified.

The step of having the automated ophthalmic eye testing device repeat atleast portions of the testing procedures when the subject's gazelocation 36 differs from the predetermined visual fixation target 32 byan amount greater than a predetermined threshold amount 34 may be at thediscretion of the clinician, who in real time during the test (or insetting up the system operation for the test) can indicate that it isdesired to obtain validated data and the testing should continue. Therepeating of the testing procedure may be of individual segments or itmay require restarting from the beginning depending upon the particularprotocol. The system may allow the clinician to selectively override there-running of the testing protocol, such as where the clinician believesthat sufficient data has been collected despite the non-compliance orwhere the clinician believes further data collection may becounterproductive due to stress on the subject or a variety of possiblereasons.

As shown in FIG. 5 the predetermined threshold amount will depend uponthe particular eye evaluation procedure and the associated desire foraccuracy for valid results. For example peripheral vision testing mayhave a threshold 34 of greater than about one degree, while retinal eyesegment mapping procedures will have a threshold 34 much less than onedegree.

Two relative thresholds 34 are shown in FIG. 5. As illustrated thecalculated gaze positions 36 shown will have two data points within thebroader threshold 34 and the present system will validate the testingresults for those two data points using the broader threshold 34 whileindicating to the clinician that the third is not a valid result and/orrerunning the testing protocol for the third data point until acceptableresults are obtained (i.e. until the gaze point 36 calculated for theassociated data is within the broader threshold 34). The test associatedwith the narrower threshold will analogously only validate the one datapoint and indicate to the clinician that the subject's gaze location 36differs from the predetermined visual fixation target 32 by an amountgreater than the predetermined threshold amount 34 for the two outlayingdata points, and/or the system will have the automated ophthalmic eyetesting device repeat at least portions of the testing procedure for thetwo non-complying data point where the subject's gaze location 36differs from the predetermined visual fixation target 32 by an amountgreater than the predetermined threshold amount 34. Additionally, notonly may the threshold 34 differ from test to test, the threshold neednot be the same in all directions (i.e. not represented as a circlearound the fixation target 32). For example compliance may be morerestrictive along one axis than the other resulting in an ellipticaltype shape for the predetermined threshold amount 34.

The system and method for validating testing procedures in objectiveophthalmic eye testing requiring subject 5 compliance with a fixationtarget may have the predetermined visual fixation target 32 supplied ata static location throughout the testing procedure. However it isanticipated that the predetermined visual fixation target 32 supplied atpredetermined varied locations throughout the testing procedure. Themoving of the fixation target 32 throughout a testing procedure canyield more complex eye evaluation procedures. Additionally someconventional tests, such as a swinging flashlight test, use what can betermed as a moving fixation target. A moving fixation target 32 may beused with a stimulus that is necessary to maintain tight control overthe shape and/or lumen and/or color of the stimulus. Using a movingfixation target 32 can allow the stimulus to be maintained in the samelocation and thus help maintain stimulus consistency which could beparticularly beneficial in retinal/eye mapping protocols wherein themapping is of the response to distinct portions of the eye beingsubjected to the same stimulus.

It is important to emphasize that the present method and associatedapparatus deals with eye evaluations requiring subject compliance witheye fixation to a visual target 32. These tests are distinctly differentfrom testing protocols that are actually measuring eye response in theform including gaze distance from a stimulus target, such as a smoothpursuit test, in which the subject's inability to maintain visual gazeon the stimulus target does not invalidate the test (but actually ispart of the desired data results of the testing protocol). The presentmethod and apparatus are directed to that family of tests in which themeaningful test data assumes and requires the subject compliance withmaintaining gaze on the target 32. Further there are tests in which thetarget 32 is only relevant for a portion of the testing protocol, andthe present method and apparatus operate as described for that portion.For example one spontaneous nystagmus test requires the subject to focuson a target 32 which will disappear and the testing is viewing the driftof the eye from the position where the target 32 was presented. In thistesting procedure the validation step of the invention is at thebeginning of the test while the target 32 is visible.

The apparatus and method for validating testing procedure in objectiveophthalmic eye testing according to invention, may in some testingprotocols, have the predetermined visual fixation target 32 form thestimulus for at least a portion of the testing procedure, such as aswinging flashlight test. The system 10 may further record pupillaryresponses of the subject's eyes 7 during at least the supplying of thepredetermined visual fixation target 32 to the subject 5. The videobased eye tracking system 10 can further record physiologic data, suchas head position or any desired data, in addition to gaze 36 of thesubject's eyes 7 during at least the supplying of the predeterminedvisual fixation target 32 to the subject 5.

STABLE PUPILLOMETRY PARAMETERS

Pupil measurements as objective ophthalmic eye testing results are wellknown and a number of standard tests are utilized to evaluate pupilaryresponse. A VOG system 10 provides objective results to such testing.FIGS. 6 and 7 are eye position graphs 40 relative to time illustratingpupilometry parameters (52, 54, 56 and 58) obtained for measuring andanalyzing ocular response with the system 10 according to one embodimentof the present invention. Conventional pupilometry measurements in theart include generally the amplitude 56 of the change to pupil size(diameter), i.e. what is the size of the pupil after stimulation orafter the stimulation is removed, or even more basically whether such achange is occurring at all, and occasionally the latency 52 of theresponse is included.

The present invention provides that constriction 54 and re-dilation 58velocity of pupil are more stable biomarkers than previously utilizedparameters. The re-dilation 58 may also simply be referenced as adilation velocity 58 of the pupil. Pupil constriction 54 and re-dilation58 velocities are radial pupil rate of change measurements. High speedVideo Oculography, wherein high speed means at least 60 hz, typically atleast 100 hz (and 250 hz and 500 hz systems are currently available)allows for measuring constriction 54 and re-dilation 58 velocity ofpupil. Pupil constriction and re-dilation acceleration, which is thederivative of constriction 54 and re-dilation 58 velocity curves is alsoa relevant bio-indicators and believed to represent further stablebio-indicator for Pupilometry measurements, although accuratePupilometry acceleration measurements may require higher operatingsample camera/system speeds of 250 Hz or more.

Pupil constriction 54 and re-dilation 56 velocity much more stable thanamplitude 56 of dilation or pupil response latency 52, which is timebetween the beginning 42 of the stimulus 44 and eye movement. As shownin FIGS. 6 and 7 it can be helpful if the stimulus 44 is graphed alongwith eye position so that the beginning 42 time and the ending 46 timeof the stimulus is readily observed on the chart, however is such dualgraphing the horizontal axis for the stimulus will typically not be eyeposition but another parameter, such as lumens or brightness of thestimulus. Additionally the pupil constriction 54 and re-dilation 58velocity and acceleration parameters can be considered more sensitivebiomarkers for evaluation purposes. These velocities 54, 58 andacceleration calculations will improve with higher speeds up to around500 hz, with diminishing returns on improved velocity or accelerationcalculations after that as these speeds far exceeds the measuredresponse. As noted the system 10 typically records each eye 7 responseof a subject 5 individually.

FIG. 8 is an eye saturation graph 60 illustrating pupilometry parameters(62, 64, 66) associated with pupil dilation velocities and stimulationillumination which are obtained for measuring and analyzing ocularresponse with the system 10 according to one embodiment of the presentinvention. Essentially the eye saturation data found in graph 60 for agiven eye 7 of a subject is found by providing a number of stimuli,individually, to the subject at increasing illumination amounts(increasing lumens or brightness). As shown in FIG. 8, for very lowilluminations (i.e., dim stimulus) the subject's eye 7 will not exhibitsignificant constriction velocity 54, until the stimulus reaches acontraction threshold illumination 62, above which each stimuli willgenerate a position graph similer to that shown in FIGS. 6-7 (withoutre-dilation). The precise contraction threshold illumination 62 may beselected as the inflection point in the graph 60 or after when a givenconstriction velocity is obtained, or a given rate of change of thevelocity, all of which will be generally known to those of ordinaryskill in the art in parsing similer physiologic parameter data. From thepoint of the contraction threshold illumination 62 the eye response toincreasing lumens or brightness of the stimuli will yield a faster pupilconstriction velocity (shown as negative values in FIG. 8 as it is forconstriction) until about the saturation point which corresponds to astimulus illumination at the dilation transition illumination 66 and amaximum (absolute) constriction velocity identified as the dilationtransition velocity 64. The precise location of the saturation point maybe at the lower inflection point of the curve, or where the curvereaches a predetermined shallowness, which precise calculation willgenerally be known to those of ordinary skill in the art. The graphs 60will typically be done for each of the subject's eyes 7.

The saturation based pupilometry parameters 62, 64, and 66 may beparticularly helpful is addressing certain characteristics, such asobjectively identifying light sensitivity of a subject 5. Further largedisparities between left and right eyes 7 of a subject of the curve 60and associated parameters 62, 64 and 66 is indicative of issues to beaddressed with the subject 5, for example it can be used as a reliableindicator of mTBI for those who have experienced head trauma. A largercontraction illumination threshold 62 will objectively identify visionissues, possibly before other testing does so. The relative values ofthe dilation transition velocity 64 and the dilation transitionillumination 66 can also be valuable biomarkers as these objectivelymeasure the effective pupil velocity limits at which the subject's eye 7can react, and the illumination at which such is reached.

The method of measuring and analyzing an ocular response in a subject 5using stable pupilary parameters includes providing a video oculographybased system 10 for the subject 5 with the video oculography systemconfigured to collect eye images of the subject 5 in excess of at least60 hz and configured to resolve eye movements smaller than at least 3degrees of motion. As discussed above, higher camera 12 speeds andgreater accuracy in measurement is preferred, subject to costconsiderations. Providing a system 10 configured to resolve eyemovements smaller than at least 2 degrees of motion or even smaller than1 degrees of motion is also preferable subject to costs and processingspeeds. The system 10 shown in FIGS. 3-4A-B provides a system operatingabove 200 Hz (240 Hz) and configured to resolve eye movements smallerthan at least 0.1 degrees of motion.

The apparatus and method of the invention provides for collecting eyedata with the video oculography based system 10 wherein at least onestimulus is presented to the subject 5 and configured to yield a pupileye response from at least one eye 7 of the subject 5. The apparatus andmethod of the invention calculates pupilometry measurements (40, 52, 54,56, 58, 60, 62, 64 and 66).

The pupilometry measurements include average pupil constriction velocity54 for subject's eyes 7, wherein the average pupil constriction velocity54 for subject's eyes is the average of the subject's eyes totalamplitude of pupil constriction 56 following a stimulus display dividedby the length of time (from 52 to 56) the associated pupil is undergoingconstriction following the start 42 of the stimulus display. Thepupilometry measurements include maximum pupil constriction velocity(also marked as 54) for subject's eyes, wherein the maximum pupilconstriction velocity 54 for subject's eyes is the maximum calculatedpupil constriction velocity 54 of the subject's eyes 7 following astimulus display. The maximum pupil constriction velocity 54 can beconsidered to be the maximum slope of the curve 54. Other methods ofcalculating and implementing pupil constriction velocity 54 are possiblesuch as dividing the curve 54 into discrete segments and using theaverage constriction velocity for each segment.

The pupilometry measurements include average pupil dilation velocity 58for subject's eyes 7, wherein the average pupil dilation velocity 58 forsubject's eyes 7 is the average of the subject's eyes 7 total amplitudeof pupil dilation following the end 46 of a stimulus display 44 dividedby the length of time the associated pupil is undergoing dilationfollowing the termination of a stimulus display. The pupilometrymeasurements include maximum pupil dilation velocity 58 for subject'seyes 7, wherein the maximum pupil dilation velocity 58 for subject'seyes 7 is the maximum calculated pupil dilation velocity 58 of thesubject's eyes following the termination of a stimulus display. Themaximum pupil dilation velocity 58 can be considered to be the maximumslope of the curve 58. Other methods of calculating and implementingpupil dilation velocity 58, like constriction velocity 54, are possiblesuch as dividing the curve 58 into discrete segments and using theaverage constriction velocity for each segment.

The pupilometry measurements include the pupil constriction accelerationfor subject's eyes 7, wherein the pupil constriction acceleration forsubject's eyes is the rate of change of the calculated pupilconstriction velocities 38 following the stimulus display 44. Thepupilometry measurements include pupil dilation acceleration forsubject's eyes 7, wherein the pupil dilation acceleration for subject'seyes 7 is the rate of change of the calculated pupil dilation velocities38 following the termination of a stimulus display. The accelerationparameters obviously cannot be based upon the average velocityparameters discussed above or an acceleration of zero will result, andnot be particularly meaningful.

The pupilometry measurements include at least one pupil saturationparameter (60. 62, 64 and 66), wherein each pupil saturation parameterfor subject's eyes 7 is a physiologic measurement associated with pupildilation velocity 58 when the eye is subjected to a stimulus 44 of agiven illumination. Preferably the maximum constriction velocity 54discussed above is used for developing the curve 60 and the associatedpupil saturation parameters 62, 64 and 66, however average constrictionvelocity could also be utilized.

The method and associated apparatus of the present invention providesfor analyzing a subject's ocular response based upon at least one of thecalculated pupilometry measurements disclosed herein.

The method and associated apparatus of measuring and analyzing an ocularresponse in a subject according to the invention may provide that thepupil measurements are calculated independently for the subject's leftand right eyes 7 for each stimulus presented to the subject. The methodof measuring and analyzing an ocular response in a subject 5 accordingto the invention may further including the step of calculatingcomparative left and right pupilometry measurements from the eye dataincluding at least one of: i) comparative pupil constriction velocityfor subject's eyes, wherein the comparative pupil constriction velocityfor subject's eyes is the difference or ratio between the subject'scalculated left eye average pupil constriction velocity and thesubject's right eye average pupil constriction velocity following thestimulus display; ii) comparative pupil dilation velocity for subject'seyes, wherein the comparative pupil dilation velocity for subject's eyesis the difference or ratio between the subject's calculated left eyeaverage pupil dilation velocity and the subject's right eye averagepupil dilation velocity following the termination of the stimulusdisplay; iii) comparative maximum pupil constriction velocity forsubject's eyes, wherein the comparative maximum pupil constrictionvelocity for subject's eyes is the difference or ratio between thesubject's calculated maximum pupil constriction velocity of thesubject's left eye and subject's calculated maximum pupil constrictionvelocity of the subject's right eye following a stimulus display; iv)comparative maximum pupil dilation velocity for subject's eyes, whereinthe comparative maximum pupil dilation velocity for subject's eyes thedifference or ratio between the subject's calculated maximum pupildilation velocity of the subject's left eye and subject's calculatedmaximum pupil dilation velocity of the subject's right eye following thetermination of the stimulus display; v) comparative pupil constrictionacceleration for subject's eyes, wherein the comparative pupilconstriction acceleration for subject's eyes is the difference or ratiobetween the subject's calculated pupil constriction acceleration of thesubject's left eye and subject's calculated pupil constrictionacceleration of the subject's right eye following the stimulus display;vi) comparative pupil dilation acceleration for subject's eyes, whereinthe comparative pupil dilation acceleration for subject's eyes is thedifference or ratio between the subject's calculated pupil dilationacceleration of the subject's left eye and subject's calculated pupildilation acceleration of the subject's right eye following terminationof the stimulus display; and vii) at least one comparative pupilsaturation parameter for subject's eyes, wherein the comparative pupilsaturation parameter for subject's eyes is the difference or ratiobetween the subject's calculated pupil saturation parameter of thesubject's left eye and subject's calculated pupil saturation parameterof the subject's right eye. Further, the step of analyzing a subject'socular response is based upon at least one of the calculated comparativepupilometry measurements.

As discussed further below, the method and associated apparatus ofmeasuring and analyzing an ocular response in a subject according toinvention may provide that each stimulus 44 is presented to only one eye7 of the subject 5 while the parameters are obtained from both.

The method of measuring and analyzing an ocular response in a subjectaccording to invention may further including the step of calculatingcomparative constriction-dilation pupilometry measurements from the eyedata including at least one of: i) comparative pupilconstriction-dilation velocity for subject's eyes, wherein thecomparative pupil constriction-dilation velocity for subject's eyes isthe difference or ratio between the subject's calculated average pupilconstriction velocity and the subject's calculated average pupildilation velocity following the stimulus display; ii) comparativemaximum pupil constriction-dilation velocity for subject's eyes, whereinthe comparative maximum pupil constriction-dilation velocity forsubject's eyes is the difference or ratio between the subject'scalculated maximum pupil constriction velocity of the subject's eyes andsubject's calculated maximum pupil dilation velocity of the subject'seyes following a stimulus display; and iii) comparative pupilconstriction-dilation acceleration for subject's eyes, wherein thecomparative pupil constriction-dilation acceleration for subject's eyesis the difference or ratio between the subject's calculated pupilconstriction acceleration of the subject's eyes and subject's calculatedpupil dilation acceleration of the subject's eyes following a stimulusdisplay. The method of measuring and analyzing an ocular response in asubject according to invention may provide that the step of analyzing asubject's ocular response is based upon at least one of the calculatedcomparative pupilometry measurements.

VIDEO OCULOGRAPHY MONITORING BOTH EYE PUPILLOMETRY WITH STIMULUS IN ONLYONE EYE

High speed Video Oculography allows for measuring response in both eyes7 while stimulating only a single eye 7 of the subject 5. Essentiallythe non stimulated eye 7 is occluded, but VOG systems 10 can obtain eyeresponses from such non stimulated eye 7 during the testing protocols.The present invention provides monitoring eye response relative to eachother as only a single eye is being stimulated and a comparison of theresponses, such as a ratio of values and/or a difference of values. Thenon-stimulated eye response parameters and comparisons of such to thestimulated eye parameters represent a significant biomarker andindicator of area of damage of neural network.

The stimulus to the one eye 7 may be visual (44) as generally known, ormay also be a pressure stimulus or a temperature stimulus orcombinations thereof. The pupilary parameters to be compared between thestimulated eye response and the response of the non stimulated eyeinclude amplitude of pupilary response, latency of the pupilaryresponse, velocity of pupilary constriction and re-dilation andacceleration of pupilary constriction and re-dilation. The comparisonparameter may be either (1) the difference between the two, i.e. thevalue of the stimulated eye minus the value of the non stimulated eyefor each parameter, or (2) the ratio between the two, i.e. the value ofthe stimulated eye divided by the value of the non stimulated eye foreach parameter (or the inverse).

HIGH SPEED VOG SYSTEM 10 SYNCHRONIZATION

Many of the above described physiologic test parameters, that couldserve as effective stable biomarkers, represent physiologic parametersonly obtainable with a high speed devices, and thus only became possiblein VOG systems 10 with cost effective high speed cameras. Theseparameters, and other “high speed parameters” such as second order orhigher corrective saccadic eye movements, micro-saccades, etc, raise anew issue with such systems, namely the synchronization of the actualtiming of the visual stimulus with measurements associated with thattiming.

Basically these high speed parameters can become inaccurate due to theprocessing elays within the conventional computer without asynchronization system. The present invention allows accurate costeffective syncrhonization of the acquired eye images with thepresentation of stimuli on a screen 22. This synchronized timing iscritical for measuring accurate high speed latencies, velocities andcertainly accelerations.

The present invention proposes several simple synchronization protocolsthat are particularly cost effective. FIG. 9A-C schematicallyillustrates system synchronization configurations for use with thesystem according to the present invention. Turning to FIGS. 9A and 9B,the OLED mciro-displays 22 used in the onboard display application aredriven by a VGA signal 72 from the controller 70 (in an associated PC).The VGA signal 72 contains red, green, and blue image components andFIG. 10A schematically illustrates a video representation of the videosynchronization signal 72 for use with the system according to onembodiment of the present invention. The present synchronization systemdiverts one of the lines, i.e. the “blue line”, to the timing comparisonunit 90, also called a custom synchronization board (comprised of thesynchronization logic module and the packet generation module as hown inFIG. 9B). Whenever the system 10 indicates a stimulus is to be outputfrom the controller 70 (PC) to present on-screen 22 to the subject 5,such as a red dot for a saccades test, the synchronization method of theinvention can render video synchronization signal 72 with a large bluebar (or any visible element) in the background as the synchronizationindicia. As shown in FIGS. 9A and B, the synchronization portion 74 (theblue portion of the signal) of the ideo synchronization signal 72 isdiverted to the timing comparison unit 90. The timing comparison unit90, also referenced as the synchronization board, sees the voltage inthe blue-signal line increase via signal 74 and is configured to outputa logic signal indicating this signal.

This logical signal from the timing comparison unit 90 (the blue-syncboard) is paired with the eye images and other data and returned to thecontroller 70 (PC) for analysis as shown in FIG. 9C The controller 70renders video based synchronization signals (72, 74), e.g. the bluebars, at key moments during testing so the system can accuratelydetermine, exactly when the visual stimulus (the dot) reaches the end ofits travel in a smooth pursuit test or appears on-screen 22 in areaction-time test. The subject does not see the blue bar syncronizationindicia because the blue color line 74 has been diverted to only thecustom synchronization board. Variations of this invention could use theother color lines or could maintain the ability to display the coloron-screen to the subject.

This synchronization method, called the blue sync method herein, isindependent of other synchronization schemes implemented and can beutilized alone to synchronize VOG systems. However the present inventiondiscloses two other synchronization methodologies that each may be usedin conjunction with the blue sync method or used independently. Each ofthese methodologies are shown in FIG. 9A.

This system provides independent synchronization through the use of aphotodiode 81 attached to the display screen 22. The controllerrendering the stimulus display in signal 76 will create visiblesynchronization pulses that the photodiode 81 will pick up generally assignal 80 in FIG. 9A. The synchronization pulses in signal 76 and thephotodiode are preferably directed to portions of the display 22 outsidethe field of view of the subject 5. Photodiode output is directed vialine 82 to the timing comparison unit 90 and is combined with the imagesfrom cameras 12 and also combined with the data from the motion sensor20 as part of the data packet that this system outputs to the computercontroller 70. This means is that data collected from the motion sensor20 and data collected from the eye via cameras 20 can then be aligned tothe stimulus data so that accurate calculations can be performed by thecontroller.

The photodiode 81 provides an advantage of additional functionality,namely the ability to calibrate the screen brightness using thephotodiode 81 coupled to a brightness controller 94 (which is separatefunctionally from the timing comparison unit 90 but may be considered apart thereof) to ensure that the screen 22 is also set to a correctbrightness. This can help correct for aging screens 22 and is importantfor light reflex tests and pupil saturation tests which rely on thelight output of the screen 22. The rate at which the data packets aresent to controller 70 is controllable from a range of every 255 ms to 1ms. This means the output rates of up to 1000 Hz is possible. Thisallows for as accurate photodiode 81 sampling as possible.

The photodiode-timing comparison unit synchronization can operateindependently of the blue sync method discussed above, or in conjunctiontherewith. If used in conjunction with each other the sync logic willprioritize the distinct timing signals 74 and 82.

This system provides third synchronization through the use of aphotodiode 81 attached to the display screen 22, in which the signal 80from the photodiode is paired via signal 84 to the eye data in camera 12via a general purpose input pin on the digital camera 12 that istracking the eye. In this synchronization scheme the images from thecamera will have the synchronization signals 84 from the photodiodeincorporated therein and the packet structure will include the embeddedsynch signals in the video image from the camera at line 86. Thephotodiode signal embedded in camera output synchronization method canoperate independently of the blue sync method discussed above, or inconjunction therewith. Further, although a common photodiode 81 is usedin both, the photodiode signal embedded in camera output synchronizationmethod is considered independent from the photodiode-timing comparisonunit 90 synchronization method as each can be individually used or usedin conjunction. If used in conjunction with each other the controllerwill prioritize the distinct timing signals added in the packet data 92and embedded within the camera image thereon.

Each of these synchronization methods have distinct advantages, and thusit may be beneficial if they are used in conjunction with each other. Asan alternative to the photodiode 81, a fiber optic line may be used inits place. Like the photodiode 81 the fiber optic line 80 can run to thetiming comparison unit 90 via line 82, with some optical sensor thereinconverting the optical signals to electrical signals for the synch logicand the packet generator. Additionally the fiber optic line 80 can runvia line 84 to the camera to be embedded directly into the imagesobtained by the camera 12. The line 84 can merely go to the front of thelens in a desired location for obtaining video synchronization signals,or bypassing the lens and be directly embedded in a portion of the imageby the camera controller. The use of fiber optic line synchronizationwill allow for greater synchronization data to be added in video signal76, such as sequential numbering of the “frames” or other desiredinformation.

In summary the synchronization apparatus of the present invention may besummarized as a video oculography based neuro-otologic testing andevaluation system comprising: A base adapted to be positioned adjacentto a subject's head; At least one digital camera 12 attached to thebase, operating at least at 60 frames per second and configured to takeimages of at least one of the subject's eyes 7; A display 22 forselectively displaying visual stimulus to the subject 5; A controller 70coupled to the display 22 generating each visual stimulus to bedisplayed and coupled to each digital camera 12 and receiving andstoring data signals there from, the controller 70 configured tocalculate eye related data from the digital camera images, andconfigured to display the eye related data to users; A videosynchronization signal 72, 76, and 74 generated by the controller 70associated with each visual stimulus which identifies when the display22 is displaying the associated visual stimulus to the subject 5;Receiving and coupling the video synchronization signal with at leastthe eye data from the digital camera, wherein the received videosynchronization signal and the eye data from the digital camera areutilized by the controller 70 to synchronize calculations based upon theeye data and the visual stimulus.

The video oculography based neuro-otologic testing and evaluation systemaccording to the invention provides in one embodiment that the systemfurther includes a photodiode 81 or fiber optic line coupled to thedisplay screen 22, wherein the photodiode or fiber optic line receivesthe video synchronization signal 76 from the display 22. Thesynchronization system according to one embodiment may provide that thecontroller creates the video synchronization signals as synchronizationpulses of video display elements of the display which are received bythe photodiode or fiber optic line. The synchronization system accordingto one embodiment may provide wherein the photodiode signals 84associated with the video synchronization signals is paired to the eyedata via an input on the digital cameras 12.

The video oculography based neuro-otologic testing and evaluation systemaccording to the invention may be provided such that the controller usesdata from a photodiode 81 coupled to the display screen 22 to calibratethe brightness of the display 22.

As discussed above the synchronization system used in the videooculography based neuro-otologic testing and evaluation system accordingto invention may provide that the controller generates each stimulus viaa signal 72 containing red, green, and blue image components associatedtherewith, and wherein one of these image components forms the videosynchronization signal 74. In this embodiment a synchronization boardreceives the video synchronization signal 74, wherein thesynchronization signal 72 from the controller forms an image with avisible synchronization element in the background of the frame as thesynchronization indicia.

The synchronization of the video oculography based neuro-otologictesting and evaluation system according to invention is needed foraccurate calculations based upon the eye data and the visual stimulus ofsmall movements such as the measurement of micro-saccades; correctivesaccades; pupil velocity; and pupil acceleration.

SACCADE REACTION TIME TESTING PROTOCOL

The present invention allows for easily adding motor reaction functionand analysis function to saccade testing, and is collectively referencedherein as Saccade Reaction Time Testing.

In a conventional saccade testing a subject 5 is told to look atstimulus when it appears. Visual stimulus is presented in a position ondisplay 22 requiring saccade movement of eye. This conventional testingprovides a variety of relevant biomarkers for researchers and cliniciansto review including eye movement peak velocity (i.e. a measure of eyemovement from a static position to secondary saccade position/time),saccadic accuracy (which is a measure of the actual target or stimulusamplitude/saccadic amplitude), saccadic latency (time between stimulusand start of saccadic movement), and additional parameters associatedwith secondary or corrective saccade movements which generally requirehigher speed of the VOG such as 150 or 200 hz or higher. Theseparameters are described in U.S. Patent Publication 2012-0081666 whichis incorporated herein by reference

In saccade reaction time testing of the present invention the subject orsubject has left and right input buttons 98 as shown in rotary chair 8of FIG. 11. The subject 5 is presented with a standard saccade test viathe display 22 and if saccade stimulus moves to right from the originalorigin or fixation target the subject 5 pushes the right button 98 andif it moves to the left the subject pushes the left button 98. Theinputs from buttons 98 are directed to the controller 70 and thistesting protocol adds motor reaction function and analysis function.Test adds parameters of motor function including latency (time tillpushing button) and accuracy of direction (did subject press rightbutton?).

FIGS. 12A-F illustrates display results and control parameters 100associated with the saccade reaction time testing protocol according toone embodiment of the present invention.

Further the two buttons 98 could be unrelated to the inherent directionto increase mental function required in the testing protocol. Forexample, in increasing level of difficulty, the left and right buttons98 may relate to up and down rather than left and right and the stimuluspresented above or below a baseline or point. The left and right buttons98 may be related to Blue stimulus images and Red stimulus images,respectively, which are selectively shown as the saccadic visual target.The buttons 98 may be related to an image of elephant and house image,respectively, which are selectively shown as the saccadic visual target.The Left and Right buttons 98 may be associated with other mentalfunctions such as identifying a Noun or Verb text that is used as thesaccadic stimulus, or identifying an Even or Odd number that is used asthe saccadic stimulus or image.

The saccadic reaction time testing and the resulting parameters 100 canprovide an important tool to address neurologic function in subjects andpossibly diagnosis damage.

VIDEO OCULOGRAPHY MONITORING BOTH EYE SACCADE TESTING WITH STIMULUS INONLY ONE EYE

As noted above High speed Video Oculography allows for measuringresponse in both eyes while stimulating only a single eye. Essentiallythe non stimulated eye is occluded, but VOG systems 10 can obtain eyeresponses from such non stimulated eye during this testing. The presentinvention provides monitoring eye response relative to each other asonly a single eye is stimulated and a comparison of the responses suchas a ratio of values and/or a difference of values represents asignificant biomarker and indicator of area of damage of neural network.This stimulation of one eye only while measuring the response of botheyes is not limited to Pupillometry and is useful in other areasincluding saccadic testing and saccadic reaction time testing in thepresent invention

INDEPENDENT AND COMPARATIVE ANALYSIS OF EYES FOR GAZE TESTING ORINDEPENDENT SPONTANEOUS NYSTAGMUS TESTING

As noted above High speed Video Oculography allows for measuringresponse in both eyes, whether one or the other is stimulated or not.Gaze testing has been known, also called independent spontaneousnystagmus testing, in which a subject stares at imaginary target in dark(to avoid other stimulus) and eye drift is observed. The target 32position may be identified with a lighted dot, which is removed. Thepresent invention allows for this testing to be performed and for thesystem 10 to quantify the amount of drift of the left and right eyes 7independently with such quantification including direction, magnitude,velocity and acceleration of drift. Further the present inventionprovides for a comparison of each parameter between the left and theright eye 7. The comparison parameters may be either (1) the differencebetween the two, i.e. the value of the left eye minus the value of theright eye for each parameter (or vice versa), or (2) the ratio betweenthe two, i.e. the value of the left eye divided by the value of theright eye for each parameter (or the inverse). As discussed above thecomparison parameters are believed to be particularly usefulbio-indicators of neural damage.

OBJECTIVE ANTISACCADE TEST RESPONSE IN VOG ENVIRONMENT

The present invention provides an objective Anti-Saccadic testingresponse in a VOG environment. The Anti-Saccade test protocol is to runa saccadic type test from a stimulus standpoint but the subject 5 isinstructed to focus on a location that is in the opposite direction fromthe starting point or origin of the test as the target stimulus and thatis the same distance. For example if the target image or stimulusappears about six inches to the right of the origin or base then thesubject 5 is to focus on a spot about six inches to the left of thebase. The anti-saccade testing introduces cognitive function andsuppression characteristics to the testing protocol. Anti-Saccadetesting response in VOG environment provides objective measurements ofeye response, generally analogous to the saccade responses discussedabove, including eye movement peak velocity (i.e. a measure of eyemovement from a static position to secondary “anti-saccade”position/time), “anti-saccadic accuracy” (which is a measure of theactual target or stimulus amplitude/ anti saccadic amplitude),anti-saccadic latency (time between stimulus and start of saccadicmovement or anti-saccadic movement), and additional parametersassociated with secondary or corrective saccade movements. Additionally,the eye movement response may break out initial non-suppressed movementstoward the saccadic image as “unsuppressed” eye movement and begin theanti-saccade measurement calculations at the point when the subjectbegins to move to the “anti-saccade position.”

Further the present invention provides a comparison of anti-saccademovement parameters for each eye and includes the stimulation of one eyeonly while measuring the response of both eyes in this anti-saccadictesting testing in the present invention.

The parameters of interest include Anti-saccade peak eye velocity(separately for left and right eye); Anti-saccade latency (separatelyfor left and right eye); Anti-saccade accuracy (separately for left andright eye); Anti-saccade overall accuracy (separately for left and righteye); Pro-saccade error (measure of error toward stimulus); and Absoluteposition error

FIGS. 13A-B illustrate display results and control parameters, generally110, associated with an objective anti-saccade test response testingprotocol according to one embodiment of the present invention. FIG. 13 Aillustrates the representative results of this testing on a subject 5while FIG. 13B illustrates a representative error rate for the subject 5in the testing protocol.

PREDICIVE SACCADE TESTING PROTOCOL IN VOG ENVIRONMENT

Saccadic testing in a VOG environment is discussed in general above. Ingeneral the saccade testing utilizes random stimulus position (oftenalong a defined axis, most often horizontal, sometimes vertical,possibly oblique). The present invention provides a test using thesaccadic protocol except that the saccadic images will repeat inposition after a given period of time, or more precisely after a givennumber of images, generally between 2 and 10, and more likely between 2and 5 images. The parameters obtained in this predictive saccade testinginclude all of those discussed above in connection with saccadictesting.

Additionally the present invention will differentiate the results witheach cycle. The main parameter of interest in the predictive saccade isthe latency parameter, and how this changes with each cycle. The dwelltime of each stimulus or image is also important for this test. Thistest results in a new biomarker or physiologic parameter, namely ameasure of the number of cycles to predict each stimulus. This parameteris equal to the number of times until the latency parameter for a givenstimulus is “less than” the stimulus origination time meaning thesubject is predicting or anticipating the stimulus position. Varying thenumber of images and dwell time of each image is expected to vary theresults for each subject. The system will also calculate the latency ofresponsive saccades that occurs after the pattern begins and also afterthe first predictive saccade.

As with the above, comparing the eye response together both when botheyes are stimulated and when one eye is occluded is included in theparameters maintained in the invention. FIGS. 14A-D illustrate displayresults and control parameters, generally 120, associated withPredictive saccade response testing protocol according to one embodimentof the present invention. It is believed a subject will have a personalpattern of predictive VS responsive that will preserver in postconcussion but will have differing latencies.

% OF SACCADE FUNCTION OF A SMOOTH PURSUIT TEST AS INDICATOR FOR MTBI

The present invention provides for a calculation of % of saccadefunction of a smooth pursuit test as indicator for mTBI, initiation timealso a critical factor for mTBI, slow and fast target speeds helpful inmTBI diagnostic, such as 0.1 hz (6.2 degrees/ second) and 1 hz (62degrees/second) rior art is out there for general presentation of % ofsaccade function. FIG. 15 illustrates display results and controlparameters, generally 130, associated with a normal and abnormalresponse in a percent of saccade function of a smooth pursuit testingprotocol which may be utilized as an indicator for mTBI according to oneembodiment of the present invention.

VIDEO OCULOGRAPHIC QUANTIFICATION OF THE FAST PHASE OPTOKINETICSTIMULATED NYSTAGMUS IN HEALTHY SUBJECTS

One aspect of the present invention includes providing an effective toolto analyze the relation between amplitude and the fast phase peakvelocity (FPV) and intra and inter individual variability of optokineticgenerated nystagmus (OKN) for healthy individuals (normals), and toevaluate the clinical utility of such normative data to permitidentification of statistically significant differences between controlsand subjects who have had a recent concussion (mTBI).

The stimulus in such a test may be an alternating black and whitevertical striped pattern moving clockwise (CW) and counterclockwise(CCW) in the yaw plane at 20 deg/sec. (d/s) and 60 d/s in an immersiveenvironment: 90% or more of the visual field, in a “stare” mode. Peakfast phase velocity shall be recorded with each subject tested in twodistinct sessions with a video-oculography(VOG) “bright-pupil” systemconnected by “fire-wire” to a computer and sampled at a rate of 100 Hz.

As early as the 1970s, the study of SPV in the animal model resulted ina quantitative analysis of its velocity characteristics. Anelectrooculography montage (EOG) recorded eye movements which weredifferentiated by amplifiers with a 3 msec. time constant and rectifiedto get the slow phase velocity without mention of the system samplerate. (Cohen, 1977) By the 1980s, the focus had broadened to evaluationof the clinical utility of assessing FPV, both peak and symmetry, insubjects with central pathology as compared to a normal control groupN=20. Subjects were in an immersive environment with EOG capture with asample rate of 200/sec. The velocity was reduced significantly insubjects with unilateral lesions in thalamus, midbrain and pons and thatfor these regions as well as the medulla and cerebellum there was adirection asymmetry of velocity which was level dependent. The authorsconcluded that the quantitative evaluation of velocity may offer,“important information on the mapping of lesions in patients with CNSdisorders.” (Kanayama, Kato, Nakamura, & Koike, 1987).

Chiba reported in 1989 the largest control group N=834 with an age rangeof 11 to 82 that evaluated a parameter of FPV: mean eye velocity. EOGrecorded eye movements: the amplifier time constant, degree of immersiveenvironment and sample rate were not included. He found no significantdifference in average or normal deviation in subjects ages 11-49. In thenext decade, the utility of such analysis was supported by data whichidentified below normal FPV, defined as two standard deviations fromChiba's norms, as characteristic of pontine level lesions. (Yamada,1991). Commercial video eye tracking systems: video-oculography(VOG)became available in North America in the mid-1980s and by the end of thefirst decade of the twenty-first century had been, “adopted by severalmanufacturers of vestibular testing equipment due to their reliability,precision, patient comfort and ease of use.” (Jacobson Gary P. &McCaslin Devin L., 2008)

This invention provides a tool a comprehensive analysis of multipleparameters of FPV as recorded with VOG to establish normative data asthe literature is not replete with such reports. The effort to establishsuch norms, to provide a standard against which a subject population maybe measured, appears justified in that previous reserachers, albeitemploying a limited FPV analysis with EOG, found it a useful tool toevaluate central function. The present invention provides an effectivebiomarker in the ratio of the velocity of the fast phase of nystagmus tothe velocity of slow phase of nystagmus generated by immersiveoptokinetic stimulation and uses this biomarker as an indication ofcentral oculomotor function in human subjects.

The parameters reviewed include Average slow phase velocity andasymmetry for slow phase Average fast phase velocity and asymmetry forfast phase and following is a representative slow phase eye velocityresponse. FIGS. 16A-D illustrate display results and control parameters,generally 140, associated with video oculographic quantification of thefast phase optokinetic stimulated nystagmus testing protocol accordingto one embodiment of the present invention.

CONCLUSION

The present invention provides tools for clinicians, researchers, andcaregivers that can be used in a number of distinct applications. Forexample consider eye tracking of younger and elderly people inassociation with the task of walking. Elderly subjects depend more onfoveal vision than younger subjects during walking. Their walking speedis decreased by a limited visual field, probably caused by adeteriorated peripheral vision. Younger subjects make use of both theircentral and peripheral vision while walking. Their peripheral visionallows faster control over the process of walking. The present methodand apparatus provides tool to better explore and remediate theseissues.

Although the present invention has been described with particularityherein, the scope of the present invention is not limited to thespecific embodiment disclosed. It will be apparent to those of ordinaryskill in the art that various modifications may be made to the presentinvention without departing from the spirit and scope thereof. The scopeof the invention is not to be limited by the illustrative examplesdescribed above.

1. A method of measuring and analyzing an ocular response in a subjectcomprising the steps of: A) Providing a video oculography based systemfor the subject with the video oculography system configured to collecteye images of the subject; B) Collecting eye data with the videooculography based system wherein at least one stimulus is presented tothe subject in only one eye and the system is configured to obtain eyeresponses simultaneously from both eyes of the subject; C) Calculatingmeasurements from the eye data including at least one measurement fromthe eye which is not being subjected to the stimulus; and D) analyzing asubject's ocular response based upon at least one of the calculatedpupilometry measurements of step C.
 2. The method of measuring andanalyzing an ocular response in a subject according to claim 1 whereinthe video oculography system configured to collect eye images of thesubject in excess of 70 hz and configured to resolve eye movementssmaller than at least 2 degrees of motion, and wherein the calculatedmeasurements from the eye data include pupil saturation parameters whichincludes at least one of contraction threshold illumination, dilationtransition illumination and a dilation transition velocity.
 3. Themethod of measuring and analyzing an ocular response in a subjectaccording to claim 1 wherein the video oculography system configured tocollect eye images of the subject in excess of 100 hz and configured toresolve eye movements smaller than at least 1 degrees of motion.
 4. Themethod of measuring and analyzing an ocular response in a subjectaccording to claim 1 wherein the video oculography system configured tocollect eye images of the subject in excess of 200 hz and configured toresolve eye movements smaller than at least 0.1 degrees of motion. 5.The method of measuring and analyzing an ocular response in a subjectaccording to claim 1 wherein the collecting eye data with the videooculography based system further includes wherein at least one stimulusis presented to the subject simultaneously to both eyes and the systemis configured wherein the eye measurements are calculated independentlyfor the subject's left and right eyes for each stimulus presented to thesubject.
 6. The method of measuring and analyzing an ocular response ina subject according to claim 5 further including the step of calculatingcomparative left and right pupilometry measurements from the eye dataincluding at least one of: i) comparative pupil constriction velocityfor subject's eyes, wherein the comparative pupil constriction velocityfor subject's eyes is the difference or ratio between the subject'scalculated left eye average pupil constriction velocity and thesubject's right eye average pupil constriction velocity following thestimulus display; ii) comparative pupil dilation velocity for subject'seyes, wherein the comparative pupil dilation velocity for subject's eyesis the difference or ratio between the subject's calculated left eyeaverage pupil dilation velocity and the subject's right eye averagepupil dilation velocity following the termination of the stimulusdisplay; iii) comparative maximum pupil constriction velocity forsubject's eyes, wherein the comparative maximum pupil constrictionvelocity for subject's eyes is the difference or ratio between thesubject's calculated maximum pupil constriction velocity of thesubject's left eye and subject's calculated maximum pupil constrictionvelocity of the subject's right eye following a stimulus display; iv)comparative maximum pupil dilation velocity for subject's eyes, whereinthe comparative maximum pupil dilation velocity for subject's eyes thedifference or ratio between the subject's calculated maximum pupildilation velocity of the subject's left eye and subject's calculatedmaximum pupil dilation velocity of the subject's right eye following thetermination of the stimulus display; v) comparative pupil constrictionacceleration for subject's eyes, wherein the comparative pupilconstriction acceleration for subject's eyes is the difference or ratiobetween the subject's calculated pupil constriction acceleration of thesubject's left eye and subject's calculated pupil constrictionacceleration of the subject's right eye following the stimulus display;vi) comparative pupil dilation acceleration for subject's eyes, whereinthe comparative pupil dilation acceleration for subject's eyes is thedifference or ratio between the subject's calculated pupil dilationacceleration of the subject's left eye and subject's calculated pupildilation acceleration of the subject's right eye following terminationof the stimulus display; and vii) at least one comparative pupilsaturation parameter for subject's eyes, wherein the comparative pupilsaturation parameter for subject's eyes is the difference or ratiobetween the subject's calculated pupil saturation parameter of thesubject's left eye and subject's calculated pupil saturation parameterof the subject's right eye.
 7. The method of measuring and analyzing anocular response in a subject according to claim 6 wherein the step ofanalyzing a subject's ocular response is based upon at least one of thecalculated comparative pupilometry measurements.
 8. (canceled)
 9. Themethod of measuring and analyzing an ocular response in a subjectaccording to claim 5, further including the step of calculatingcomparative constriction-dilation pupilometry measurements from the eyedata including at least one of: i) comparative pupilconstriction-dilation velocity for subject's eyes, wherein thecomparative pupil constriction-dilation velocity for subject's eyes isthe difference or ratio between the subject's calculated average pupilconstriction velocity and the subject's calculated average pupildilation velocity following the stimulus display; ii) comparativemaximum pupil constriction-dilation velocity for subject's eyes, whereinthe comparative maximum pupil constriction-dilation velocity forsubject's eyes is the difference or ratio between the subject'scalculated maximum pupil constriction velocity of the subject's eyes andsubject's calculated maximum pupil dilation velocity of the subject'seyes following a stimulus display; and iii) comparative pupilconstriction-dilation acceleration for subject's eyes, wherein thecomparative pupil constriction-dilation acceleration for subject's eyesis the difference or ratio between the subject's calculated pupilconstriction acceleration of the subject's eyes and subject's calculatedpupil dilation acceleration of the subject's eyes following a stimulusdisplay.
 10. The method of measuring and analyzing an ocular response ina subject according to claim 9 wherein the step of analyzing a subject'socular response is based upon at least one of the calculated comparativepupilometry measurements.
 11. A method of measuring and analyzing anocular response in a subject comprising the steps of: A) Providing avideo oculography based system for the subject with the videooculography system configured to collect eye images of the subject; B)Collecting eye data of both eyes of the user with the video oculographybased system wherein at least one stimulus is presented to the subjectand configured to yield an eye response from at least one eye of thesubject; C) Calculating left eye response measurements from the eyedata; D) Calculating right eye response measurements from the eye data;and E) analyzing a subject's ocular response based upon at least one ofthe calculated left eye response measurements of step C compared with atleast one of the calculated right eye response measurements of step D.12. The method of measuring and analyzing an ocular response in asubject according to claim 11 further including the step of calculatingcomparative constriction-dilation pupilometry measurements from the eyedata including at least one of: i) comparative pupilconstriction-dilation velocity for subject's eyes, wherein thecomparative pupil constriction-dilation velocity for subject's eyes isthe difference between the subject's calculated average pupilconstriction velocity and the subject's calculated average pupildilation velocity following the stimulus display; ii) comparativemaximum pupil constriction-dilation velocity for subject's eyes, whereinthe comparative maximum pupil constriction-dilation velocity forsubject's eyes is the difference between the subject's calculatedmaximum pupil constriction velocity of the subject's eyes and subject'scalculated maximum pupil dilation velocity of the subject's eyesfollowing a stimulus display; and iii) comparative pupilconstriction-dilation acceleration for subject's eyes, wherein thecomparative pupil constriction-dilation acceleration for subject's eyesis the difference between the subject's calculated pupil constrictionacceleration of the subject's eyes and subject's calculated pupildilation acceleration of the subject's eyes following a stimulusdisplay.
 13. The method of measuring and analyzing an ocular response ina subject according to claim 12 wherein the step of analyzing asubject's ocular response is based upon at least one of the calculatedcomparative pupilometry measurements.
 14. The method of measuring andanalyzing an ocular response in a subject according to claim 11 whereinthe pupil measurements are calculated independently for the subject'sleft and right eyes for each stimulus presented to the subject.
 15. Themethod of measuring and analyzing an ocular response in a subjectaccording to claim 14 further including the step of calculatingcomparative left and right pupilometry measurements from the eye dataincluding at least one of: i) comparative pupil constriction velocityfor subject's eyes, wherein the comparative pupil constriction velocityfor subject's eyes is the difference between the subject's calculatedleft eye average pupil constriction velocity and the subject's right eyeaverage pupil constriction velocity following the stimulus display; ii)comparative pupil dilation velocity for subject's eyes, wherein thecomparative pupil dilation velocity for subject's eyes is the differencebetween the subject's calculated left eye average pupil dilationvelocity and the subject's right eye average pupil dilation velocityfollowing the termination of the stimulus display; iii) comparativemaximum pupil constriction velocity for subject's eyes, wherein thecomparative maximum pupil constriction velocity for subject's eyes isthe difference between the subject's calculated maximum pupilconstriction velocity of the subject's left eye and subject's calculatedmaximum pupil constriction velocity of the subject's right eye followinga stimulus display; iv) comparative maximum pupil dilation velocity forsubject's eyes, wherein the comparative maximum pupil dilation velocityfor subject's eyes the difference between the subject's calculatedmaximum pupil dilation velocity of the subject's left eye and subject'scalculated maximum pupil dilation velocity of the subject's right eyefollowing the termination of the stimulus display; v) comparative pupilconstriction acceleration for subject's eyes, wherein the comparativepupil constriction acceleration for subject's eyes is the differencebetween the subject's calculated pupil constriction acceleration of thesubject's left eye and subject's calculated pupil constrictionacceleration of the subject's right eye following the stimulus display;vi) comparative pupil dilation acceleration for subject's eyes, whereinthe comparative pupil dilation acceleration for subject's eyes is thedifference between the subject's calculated pupil dilation accelerationof the subject's left eye and subject's calculated pupil dilationacceleration of the subject's right eye following termination of thestimulus display; and vii) at least one comparative pupil saturationparameter for subject's eyes, wherein the comparative pupil saturationparameter for subject's eyes is the difference or ratio between thesubject's calculated pupil saturation parameter of the subject's lefteye and subject's calculated pupil saturation parameter of the subject'sright eye.
 16. The method of measuring and analyzing an ocular responsein a subject according to claim 15 wherein the step of analyzing asubject's ocular response is based upon at least one of the calculatedcomparative pupilometry measurements.
 17. The method of measuring andanalyzing an ocular response in a subject according to claim 14 whereineach stimulus is presented to only one eye of the subject.
 18. A methodof measuring and analyzing an ocular response in a subject comprisingthe steps of: A) Providing a video oculography based system for thesubject with the video oculography system configured to collect eyeimages of the subject; B) Collecting eye data with the video oculographybased system wherein at least one stimulus is presented to only one eyeof the subject and configured to yield a pupil eye response from atleast one eye of the subject; C) Calculating pupilometry measurementsfrom the eye data, wherein the pupil measurements are calculatedindependently for the subject's left and right eyes for each stimuluspresented to the subject, and wherein comparative left and rightpupilometry measurements from the eye data are calculated; D) analyzinga subject's ocular response based upon at least one of the calculatedpupilometry measurements of step C.
 19. The method of measuring andanalyzing an ocular response in a subject according to claim 18 whereinthe step of calculating pupilometry measurements from the eye dataincludes calculating at least one of: i) average pupil constrictionvelocity for subject's eyes, wherein the average pupil constrictionvelocity for subject's eyes is the average of the subject's eyes totalamplitude of pupil constriction following a stimulus display divided bythe length of time the associated pupil is undergoing constrictionfollowing the stimulus display; ii) average pupil dilation velocity forsubject's eyes, wherein the average pupil dilation velocity forsubject's eyes is the average of the subject's eyes total amplitude ofpupil dilation following a stimulus display divided by the length oftime the associated pupil is undergoing dilation following thetermination of a stimulus display; iii) maximum pupil constrictionvelocity for subject's eyes, wherein the maximum pupil constrictionvelocity for subject's eyes is the maximum calculated pupil constrictionvelocity of the subject's eyes following a stimulus display; iv) maximumpupil dilation velocity for subject's eyes, wherein the maximum pupildilation velocity for subject's eyes is the maximum calculated pupildilation velocity of the subject's eyes following the termination of astimulus display; v) pupil constriction acceleration for subject's eyes,wherein the pupil constriction acceleration for subject's eyes is therate of change of the calculated pupil constriction velocities followingthe stimulus display; vi) pupil dilation acceleration for subject'seyes, wherein the pupil dilation acceleration for subject's eyes is therate of change of the calculated pupil dilation velocities following thetermination of a stimulus display; and vii) at least one pupilsaturation parameter, wherein each pupil saturation parameter forsubject's eyes is a physiologic measurement associated with pupildilation velocity when the eye is subjected to a stimulus of a givenillumination.
 20. The method of measuring and analyzing an ocularresponse in a subject according to claim 19 wherein the step ofcalculating comparative left and right pupilometry measurements from theeye data includes at least one of: i) comparative pupil constrictionvelocity for subject's eyes, wherein the comparative pupil constrictionvelocity for subject's eyes is the difference between the subject'scalculated left eye average pupil constriction velocity and thesubject's right eye average pupil constriction velocity following thestimulus display; ii) comparative pupil dilation velocity for subject'seyes, wherein the comparative pupil dilation velocity for subject's eyesis the difference between the subject's calculated left eye averagepupil dilation velocity and the subject's right eye average pupildilation velocity following the termination of the stimulus display;iii) comparative maximum pupil constriction velocity for subject's eyes,wherein the comparative maximum pupil constriction velocity forsubject's eyes is the difference between the subject's calculatedmaximum pupil constriction velocity of the subject's left eye andsubject's calculated maximum pupil constriction velocity of thesubject's right eye following a stimulus display; iv) comparativemaximum pupil dilation velocity for subject's eyes, wherein thecomparative maximum pupil dilation velocity for subject's eyes thedifference between the subject's calculated maximum pupil dilationvelocity of the subject's left eye and subject's calculated maximumpupil dilation velocity of the subject's right eye following thetermination of the stimulus display; comparative pupil constrictionacceleration for subject's eyes, wherein the comparative pupilconstriction acceleration for subject's eyes is the difference betweenthe subject's calculated pupil constriction acceleration of thesubject's left eye and subject's calculated pupil constrictionacceleration of the subject's right eye following the stimulus display;vi) comparative pupil dilation acceleration for subject's eyes, whereinthe comparative pupil dilation acceleration for subject's eyes is thedifference between the subject's calculated pupil dilation accelerationof the subject's left eye and subject's calculated pupil dilationacceleration of the subject's right eye following termination of thestimulus display; and vii) at least one comparative pupil saturationparameter for subject's eyes, wherein the comparative pupil saturationparameter for subject's eyes is the difference or ratio between thesubject's calculated pupil saturation parameter of the subject's lefteye and subject's calculated pupil saturation parameter of the subject'sright eye.